Project Summary/Abstract The long-term objectives of this proposal are to drive the development and translation of scientific discoveries to therapeutic strategies that address a broad range of human diseases. Northwestern University?s Atomic and Nanoscale Characterization Experimental Center (NUANCE) is a well-established shared resource facility that supports the execution of diverse research projects. NUANCE houses and maintains state-of-the-art core analytical characterization instrumentation and provides open access, hands-on training, education, and outreach. Instrumentation includes several transmission electron microscopes (TEMs) including a JEOL ARM300F GrandARM TEM which allows researchers to digitally image their samples. However, many of the inorganic, organic, and biohybrid nanomaterials for biomedical applications are destroyed or cannot be imaged at all by standard TEM with currently available cameras. The acquisition of a K2-IS direct electron detection camera attachment for the existing TEM would overcome this limitation and enable unprecedented imaging of these fragile samples revealing sub-nanometer detail at low electron dose. In addition, it will enable unique liquid cell TEM imaging of these materials in water and other solvents to elucidate dynamics. This instrumentation will significantly enhance the facility?s capabilities and meet the research needs of NUANCE users. To support this instrumentation, the University has made concrete commitments toward technical staff for installation, development of curriculum materials, training, and development of advanced techniques. Acquisition of the K2- IS direct electron detection camera will allow seamless continuation of NIH-supported projects and spur the development of new therapeutic strategies for numerous diseases. Finally, this new instrumentation will significantly enhance the capabilities of this facility to support basic and translational biomedical research within Northwestern and the greater Chicago area research community.